I.L. and J.M. contributed equally to this work.
The absence of Complexin 3 and Complexin 4 differentially impacts the ON and OFF pathways in mouse retina
Article first published online: 14 JUN 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 36, Issue 4, pages 2470–2481, August 2012
How to Cite
Landgraf, I., Mühlhans, J., Dedek, K., Reim, K., Brandstätter, J. H. and Ammermüller, J. (2012), The absence of Complexin 3 and Complexin 4 differentially impacts the ON and OFF pathways in mouse retina. European Journal of Neuroscience, 36: 2470–2481. doi: 10.1111/j.1460-9568.2012.08149.x
- Issue published online: 20 AUG 2012
- Article first published online: 14 JUN 2012
- Received 23 November 2011, revised 1 March 2012, accepted 5 April 2012
- amacrine cell;
- bipolar cell;
- ganglion cell;
Complexins (Cplxs) regulate the speed and Ca2+-sensitivity of synaptic vesicle fusion. It has been shown that all four known Cplxs are present at mouse retinal synapses – at conventional amacrine cell synapses (Cplx 1 to Cplx 3) and at photoreceptor and bipolar cell ribbon synapses (Cplx 3 and Cplx 4) [K. Reim et al. (2005)J. Cell Biol.,169, 669-680]. Electroretinographic recordings in Cplx 3/Cplx 4 double-knockout (DKO) mice showed perturbed transmission in the outer plexiform layer, and possible changes in the inner plexiform layer [K. Reim et al. (2009)J. Cell Sci.,122, 1352–1361]. In the present study, we examined the effects of the absence of Cplx 3 and Cplx 4 on ganglion cell responses. We report that the lack of Cplx 3 and Cplx 4 differentially impacts the ON and OFF pathways. Under photopic conditions, the responses in the cone OFF pathway are largely unaffected, whereas the responses in the cone ON pathway are diminished in Cplx 3/Cplx 4 DKO mice. Under scotopic conditions, both ON and OFF response rates are reduced and high-sensitivity OFF responses are missing in Cplx 3/Cplx 4 DKO mice. The electrophysiological findings are corroborated by new immunocytochemical findings. We now show that rod spherules contain only Cplx 4. However, both Cplx 3 and Cplx 4 co-localize in cone pedicles. In the inner plexiform layer, Cplx 3 is present in rod bipolar cell terminals and in amacrine cell processes. Most importantly, Cplx 3 is localized in the lobular appendages of AII amacrine cells, the sites of signal transmission from the primary rod pathway into the OFF pathway in the inner plexiform layer.